Transplantation of mesenchymal stem cells to enhance engraftment of hematopoietic stem cells

被引:303
作者
Le Blanc, K.
Samuelsson, H.
Gustafsson, B.
Remberger, M.
Sundberg, B.
Arvidson, J.
Ljungman, P.
Lonnies, H.
Nava, S.
Ringden, O.
机构
[1] Karolinska Univ Hosp, Karolinska Inst, Div Clin Immunol, SE-14186 Stockholm, Sweden
[2] Karolinska Univ Hosp, Karolinska Inst, Hematol Ctr, SE-14186 Stockholm, Sweden
[3] Karolinska Univ Hosp, Karolinska Inst, Dept Pediat, SE-14186 Stockholm, Sweden
[4] Karolinska Univ Hosp, Karolinska Inst, Ctr Allogene Stem Cell Transplantat, SE-14186 Stockholm, Sweden
[5] Univ Uppsala Hosp, Dept Womens & Childrens Hlth, Uppsala, Sweden
关键词
mesenchymal stem cells (MSCs); hematopoietic stem cell transplantation (HSCT); hematopoietic engraftment;
D O I
10.1038/sj.leu.2404777
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Seven patients underwent treatment with mesenchymal stem cells (MSCs), together with allogeneic hematopoietic stem cell transplantation (HSCT). MSCs were given to three patients for graft failure and four patients were included in a pilot study. HSCT donors were three human leukocyte antigen (HLA)identical siblings, three unrelated donors and one cord blood unit. The conditioning was myeloablative in four patients and reduced in three patients. MSC donors were HLA-identical siblings in three cases and haploidentical in four cases. Neutrophil counts >0.5 x 10(9)/l was reached at a median of 12 (range 10-28) days. Platelet counts >30 x 10(9)/l was achieved at a median of 12 (8-36) days. Acute graft-versus-host disease (GVHD) grade 0-1 was seen in five patients. Two patients developed grade II, which in one patient evolved into chronic GVHD. One severe combined immunodeficiency (SCID) patient died of aspergillosis, the others are alive and well. One patient, diagnosed with aplastic anemia had graft failure after her first transplantation and severe Henoch-Schonlein Purpura (HSP). After retransplantation of MSCs and HSCs, she recovered from both the HSP and aplasia. Thus, co-transplantation of MSC resulted in fast engraftment of absolute neutrophil count (ANC) and platelets and 100% donor chimerism, even in three patients regrafted for graft failure/rejection.
引用
收藏
页码:1733 / 1738
页数:6
相关论文
共 46 条
[1]   Cotransplantation of human stromal cell progenitors into preimmune fetal sheep results in early appearance of human donor cells in circulation and boosts cell levels in bone marrow at later time points after transplantation [J].
Almeida-Porada, G ;
Porada, CD ;
Tran, N ;
Zanjani, ED .
BLOOD, 2000, 95 (11) :3620-3627
[2]   Cotransplantation of human mesenchymal stem cells enhances human myelopoiesis and megakaryocytopoiesis in NOD/SCID mice [J].
Angelopoulou, M ;
Novelli, E ;
Grove, JE ;
Rinder, HM ;
Civin, C ;
Cheng, LZ ;
Krause, DS .
EXPERIMENTAL HEMATOLOGY, 2003, 31 (05) :413-420
[3]   Failure of adult marrow-derived stem cells to generate marrow stroma after successful hematopoietic stem cell transplantation [J].
Awaya, N ;
Rupert, K ;
Bryant, E ;
Torok-Storb, B .
EXPERIMENTAL HEMATOLOGY, 2002, 30 (08) :937-942
[4]   Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong skin graft survival in vivo [J].
Bartholomew, A ;
Sturgeon, C ;
Siatskas, M ;
Ferrer, K ;
McIntosh, K ;
Patil, S ;
Hardy, W ;
Devine, S ;
Ucker, D ;
Deans, R ;
Moseley, A ;
Hoffman, R .
EXPERIMENTAL HEMATOLOGY, 2002, 30 (01) :42-48
[5]   Identification of mesenchymal stem/progenitor cells in human first-trimester fetal blood, liver, and bone marrow [J].
Campagnoli, C ;
Roberts, IAG ;
Kumar, S ;
Bennett, PR ;
Bellantuono, I ;
Fisk, NM .
BLOOD, 2001, 98 (08) :2396-2402
[6]   Effect of chemotherapy for acute myelogenous leukemia on hematopoietic and fibroblast marrow progenitors [J].
CarloStella, C ;
Tabilio, A ;
Regazzi, E ;
Garau, D ;
LaTagliata, R ;
Trasarti, S ;
Andrizzi, C ;
Vignetti, M ;
Meloni, G .
BONE MARROW TRANSPLANTATION, 1997, 20 (06) :465-471
[7]   LACK OF RECOVERY OF MURINE HEMATOPOIETIC STROMAL CELLS AFTER IRRADIATION-INDUCED DAMAGE [J].
CHAMBERL.W ;
BARONE, J ;
KEDO, A ;
FRIED, W .
BLOOD, 1974, 44 (03) :385-392
[8]   Mesenchymal stem cells home to injured tissues when co-infused with hematopoietic cells to treat a radiation-induced multi-organ failure syndrome [J].
Chapel, A ;
Bertho, JM ;
Bensidhoum, M ;
Fouillard, L ;
Young, RG ;
Frick, J ;
Demarquay, C ;
Cuvelier, F ;
Mathieu, E ;
Trompier, F ;
Dudoignon, N ;
Germain, C ;
Mazurier, C ;
Aigueperse, J ;
Borneman, J ;
Gorin, NC ;
Gourmelon, P ;
Thierry, D .
JOURNAL OF GENE MEDICINE, 2003, 5 (12) :1028-1038
[9]  
Cilloni D, 2000, BLOOD, V96, P3637
[10]   Sirolimus and tacrolimus without methotrexate as graft-versus-host disease prophylaxis after matched related donor peripheral blood stem cell transplantation [J].
Cutler, C ;
Kim, HT ;
Hochberg, E ;
Ho, V ;
Alyea, E ;
Lee, SJ ;
Fisher, DC ;
Miklos, D ;
Levin, J ;
Sonis, S ;
Soiffer, RJ ;
Antin, JH .
BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION, 2004, 10 (05) :328-336